2,6-Dibromopyridine → 6-Bromo-(4-methoxybenzylamino)pyridine

HRID 2187387Notes

Reaction equation

HRID 2187387 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[N:3]=1.[CH3:9][O:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][NH2:16])=[CH:13][CH:12]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[Br:8][C:4]1[N:3]=[C:2]([NH:16][CH2:15][C:14]2[CH:17]=[CH:18][C:11]([O:10][CH3:9])=[CH:12][CH:13]=2)[CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 122742,6-DibromopyridineHCID 754524-MethoxybenzylamineHCID 81531Diisopropylethylamine

Product 1

HCID 234355096-Bromo-(4-methoxybenzylamino)pyridineYield 91.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 2,6-dibromopyridine (14-1) (37.3 g, 157 mmol), 4-methoxybenzylamine (21.6 g, 157 mmol), and diisopropylethylamine (22.4 g, 173 mmol) in 1,4-dioxane (150 mL) was heated at reflux for 24 h. The reaction mixture was cooled, concentrated in vacuo, and the residue was partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (125 mL). The organic layer was washed with water (100 mL) followed by brine (100 mL) and dried (Na2SO4). The organic layer was filtered, concentrated in vacuo, and purified by flash chromatography (silica, 10% to 40% EtOAc/hexanes) affording 42 g of amine 14-2 as a white solid in 91% yield. 1H NMR (300 Mz, CDCl3): δ 8 7.26-7.22 (m, 3H), 6.88-6.86 (m, 2H), 6.75-6.73 (d 1H), 6.27-6.25 (d, 1H), 4.98-4.96 (br s, 1H), 4.39-4.37 (d, 2H), 3.80 (s, 3H).

Workup

  1. temperatureat reflux for 24 h
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated in vacuo
  4. customthe residue was partitioned between EtOAc (100 mL) and saturated aqueous NaHCO3 (125 mL)
  5. washThe organic layer was washed with water (100 mL)
  6. dry with materialdried (Na2SO4)
  7. filtrationThe organic layer was filtered
  8. concentrationconcentrated in vacuo
  9. custompurified by flash chromatography (silica, 10% to 40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-20ffbb7e67614ae8b003a350a9ff8bbd
Source dataset
uspto-grants-2002_06
Patent number
US06410526B1

Reaction notes

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